Prognostic value of mutations and a germ line polymorphism of the p53 gene in non-small cell lung carcinoma: association with clinicopathological features.

The prognostic value of the mutation of the p53 tumor suppressor gene in non-small cell lung carcinomas (NSCLC) is controversial and a polymorphism of the p53 gene at codon 72 consisting of two alleles, arginine (Arg) and proline (Pro), has been reported to be associated with the incidence of smoking-related NSCLC. We have studied 67 cases of NSCLC in relation to the mutation of the p53 gene by polymerase chain reaction (PCR)-single-strand conformation polymorphism and 178 cases in relation to the polymorphism of the gene by PCR using allele-specific primers. The genetic alterations of the p53 gene (from exons 5 to 9) were found in 34% of the patients. Frequent mutations were observed among younger patients (less than 65 years old), however, there is no significant correlation of the mutation with smoking history, histopathological types, clinical stages or prognosis. We observed that Arg/Arg homozygotes were frequently found in non-smoking patients with NSCLC but Arg/Pro heterozygotes were infrequent in the group. There was no significant association of the polymorphic alleles with histopathological types, clinical stages or prognosis. Thus, the polymorphism of the p53 gene affects the predisposition of non-smokers to NSCLC, but the alteration of the p53 gene is independent of tumor progression and histopathology.